The study of endometrial (uterine) cancer is important. At the present time, non-surgical treatments for this form of cancer are limited to therapy with hormones or cytotoxic agents, which are not completely effective. Previous studies from other laboratories have documented a correlation between decreased gap junction communication (gjc), which is mediated by intracellular protein channels called connexons, and carcinogenesis. Conceivably, a decreased level of gap junction (connexon) protein may contribute to abnormal regulation of epithelial cell proliferation and carcinogenesis in the human endometrium. Coculture experiments of young stromal and transformed endometrial cells have suggested that stromal cells may be secreting a diffusible factor(s) mediating reversal of the carcinogenic process. It is conceivable that coculture of malignant epithelial cells with young stromal cells may reverse their carcinogenic potential by inducing the malignant cells to re-establish normal gap junction protein levels. Western blots using antibodies against connexin 43, 32, and 26 and dye transfer assays will be used to test the validity of this hypothesis. Subsequently, 2-dimensional electrophoresis and high performance liquid chromatography analysis will be used to identify and isolate the diffusible factor(s) mediating the communication between the normal stromal and malignant epithelial cells that may be responsible for carcinogenesis reversal. A bioassay will be developed to vent this activity. Once a basic understanding of endometrial stromal and epithelial cell to cell signaling has been established, further studies will be undertaken to develop novel therapeutic approaches for the treatment of human endometrial epithelial carcinoma. Consequently, my research proposal involves translational research.